Comparison between the effect of butyric acid and its prodrug pivaloyloxymethylbutyrate on histones hyperacetylation in an HL-60 leukemic cell line

A butyric acid pro-drug, pivaloyioxymethyl butyrate, AN-9, developed in our laboratory, was previously shown to act as a differentiation-inducing and an anti-cancer agent. In this study we have shown that both AN-9 and butyric acid caused a transient hyperacetylation of histones, which returned to basal levels after 6 and 12 hr, respectively. This activity precedes the induction of differentiation elicited by both agents. AN-9 induced acetylation of histones at a concentration one order of magnitude lower than butyric acid. Pre-treatment of the cells with esterase(s) inhibitors diminished the ability of AN-9 to inhibit proliferation and induce differentiation. The above suggests that the intracellular release of butyric acid fragment, from the pro-drug, is catalyzed by cellular esterase(s).     

Sadness predicts death in older people

OBJECTIVE. To determine if a question about symptoms of depression in a mail survey predicts mortality after adjusting for a large number of covariates. DESIGN. National cross-sectional survey of 141,589 enrollees in Medicare, age 65 and older. Analyses used multivariate logistic regression models with death as the outcome. RESULTS. Response to a question about sadness or anhedonia was associated with death in 2 years (OR = 1.32; 95% CI = 1.2, 1.4). Results were consistent across age, gender, and presence/absence of known heart disease. Other responses associated with death were older age, male gender, and self-reported cancers, shortness of breath, heart failure, smoking, and other characteristics. Higher education and being married appeared to protect from death. DISCUSSION. A single survey question about feelings of sadness or anhedonia is predictive of death in 2 years.     

Sleep-wake patterns in children with intrauterine growth retardation

The purpose of this study was to characterize the sleep patterns of children with intrauterine growth retardation, known to be at risk for neurodevelopmental disorders, and seek a possible correlation with behavior, concentration, and attention problems. The sleep patterns of 26 children with intrauterine growth retardation aged 4 to 7 years were compared with those of 47 control children using activity monitors (actigraphs). In addition, data were collected from the parents regarding sleep habits, behavior, concentration, and attention. Children with intrauterine growth retardation aged 4 to 7 years were found to have a tendency toward poorer quality of sleep than their matched controls. This inclination was statistically significant only for one sleep measure, the true sleep time. A tendency toward increased fragmentation of sleep, prolonged waking, and decreased sleep efficiency, although not statistically significant in this study, was demonstrated. Our results showed that 58% of the children with intrauterine growth retardation, compared with 40% of the children in the control group, could be defined as "poor sleepers" (sleep efficiency lower than 90% or three or more waking episodes per night). This disturbed sleep profile is probably an integral part of the neurodevelopmental profile typical of these at-risk children. No significant correlations were found between sleep quality and behavior, concentration, and attention problems.     

Magnetic resonance imaging of the thalamus in male patients with schizophrenia

Thalamic abnormalities have been hypothesized to explain much of the psychopathology in schizophrenia, however, quantitative magnetic resonance imaging (MRI) studies have yielded discrepant results as to whether there are thalamic volume alterations. The current study utilized high resolution MRI and an axial voluming protocol to determine if there was a significant reduction in the volume of the thalamus in patients with schizophrenia. Quantitative analysis was performed on magnetic resonance images of the brain in 41 male medicated schizophrenic patients and 39 male normal control subjects similar in age, education and handedness. There were no group differences in thalamic volumes between controls and patients with schizophrenia, even after adjusting for intracranial volume, total brain tissue volume, and gray matter volume. There were also no significant correlations between thalamic volume and either current neuroleptic dose or illness duration. However, there was a significant right greater than left thalamic volume asymmetry in schizophrenics and controls, and the degree of thalamic volume asymmetry was similar in both groups. The failure to detect any significant difference in thalamic volumes may be due to the heterogeneity of the schizophrenic population and as yet undetermined chronic effects of neuroleptic medication on the thalamus. However, another reasonable explanation for the study findings is that quantitative MRI voluming of the entire thalamus may not be sensitive enough to detect more subtle regional neuropathology within the thalamus.     

Achieving improvement through nursing home quality measurement

CMS has initiated the Nursing Home Quality Initiative (NHQI) to improve the quality of nursing home care. Central to the NHQI is the public reporting of nursing home quality measures that serve as the basis for the Initiative's communication and quality improvement program. This article provides an overview of the NHQI, focusing on the role of nursing home quality measures in achieving improvements in nursing home care. We also describe the evolution of quality measurement in nursing homes, a recent CMS project to improve measures through risk adjustment and other refinements, the use of these measures in a pilot of the NHQI, and the lessons learned for future work in this area.     

Identification and evaluation of existing nursing homes quality indicators

We summarize work done to identify and evaluate existing quality indicators (QIs) for long-term care (LTC) settings. Indicators operationally defined using routinely collected and computerized patient assessments were identified and then aggregated to characterize the performance of the nursing facility over a specific period of time. Of 143 indicators reviewed, only 22 were recommended for use in comparing performance across facilities. Conceptual and technical issues influence the appropriateness of QIs for different audiences.     

The role of the family physician in eating disorders

The steady increase in Eating Disorders (ED) during the last three decades has raised increasing concern over the early diagnosis and treatment of this disease. Due to the multi-factorial etiology of ED, treatment is complex, prolonged, and demands a team approach. Family physicians are often approached first for consultation following the patient's initial physical complaints. For this reason, the general practitioner can play a critical role in the early diagnosis and treatment of these disorders. By asking the appropriate questions and providing relevant information, the family physician (FP) may be able to refer the patient to treatment necessary for recovery, as well as assist in this process. Because the family physician typically has previous acquaintance with the patient and her family, he or she may be of considerable import to creating a therapeutic liaison and support framework with the professional team. This article will discuss the potential involvement and significance of the family physician in the successful diagnosis, prevention, and treatment of ED. The importance of the FP in the decision for hospitalization, referral, and follow-up is emphasized, as well as the pivotal role of the FP as a multi-disciplinary team coordinator.     

Mammalian heparanase: involvement in cancer metastasis,angiogenesis and normal development

Cleavage of heparan sulphate proteoglycans (HSPGs) affects the integrity and functional state of tissues and thereby fundamental normal and pathological phenomena involving cell migration and response to changes in the extracellular microenvironment. Heparanase, degrading heparan sulphate (HS) at specific intrachain sites, is synthesized as a latent approximately 65 kDa protein that is processed at the N-terminus into a highly active approximately 50 kDa form. The heparanase enzyme is preferentially expressed in human tumours and its overexpression in low-metastatic tumour cells confers a highly invasive phenotype in experimental animals. Heparanase also releases angiogenic factors and accessory fragments of HS from the tumour microenvironment and induces an angiogenic response in vivo. Heparanase may thus facilitate tumour cell invasion, vascularization and survival in a given microenvironment, all critical events in cancer progression. These observations, the anticancerous effect of heparanase-inhibiting molecules, and the unexpected identification of a single predominant functional heparanase suggest that the enzyme is a promising target for drug development.